Changes in alcohol use and mood during the COVID-19 pandemic among individuals with traumatic brain injury: A difference-in-difference study

Objective To evaluate the impact of COVID-19 pandemic exposure on changes in alcohol use and mood from years 1 to 2 after traumatic brain injury (TBI). Methods We used a difference-in-difference (DiD) study design to analyze data from 1,059 individuals with moderate-to-severe TBI enrolled in the TBI Model Systems (TBIMS) National Database. We defined COVID-19 pandemic exposure as participants who received their year 1 post-injury interviews prior to January 1, 2020, and their year 2 interview between April 1, 2020 and January 15, 2021. Pandemic-unexposed participants had both year 1 and 2 follow-up interviews before January 1, 2020. We measured current alcohol use as any past month alcohol use, average number of drinks per drinking occasion, and past month binge drinking. We measured depression symptoms using Patient Health Questionnaire-9, and anxiety symptoms using the Generalized Anxiety Disorder-7. Results We found persons with TBI exposed to the pandemic had greater increases in the average number of drinks per occasion from year 1 to 2 post-injury compared to pandemic-unexposed individuals (β = 0.36, 95% CI: 0.16, 0.57, p = 0.001), with males, adults <65 years old, and Black and Hispanic subgroups showing the greatest increases in consumption. Though average consumption was elevated, changes in rates of any alcohol use or binge drinking by pandemic exposure were not observed. Overall, there were no significant changes in depressive and anxiety symptoms over time between pandemic exposed and unexposed groups; however, pandemic-exposed Hispanics with TBI reported significant increases in anxiety symptoms from year-1 to year-2 post-injury compared to pandemic-unexposed Hispanics (β = 2.35, 95% CI: 0.25, 4.47, p = 0.028). Conclusion Among persons living with TBI, those exposed to the pandemic had significant increases in average alcohol consumption. Pandemic-exposed Hispanics with TBI had large elevations in anxiety symptoms, perhaps reflecting health inequities exacerbated by the pandemic, and suggesting a need for targeted monitoring of psychosocial distress.


Introduction
The coronavirus disease-2019 (COVID- 19) pandemic has resulted in widespread societal consequences, including death, strained healthcare systems, and tremendous economic disruption. In addition to the direct sequelae from infection, more people worldwide are reporting increased psychological distress [1,2] and alcohol use [3,4] during the pandemic. Studies of U.S. populations have found elevated distress [5], with up to a third of individuals meeting criteria for depressive or anxiety disorders during the pandemic [6,7]. Moreover, greater psychological distress has been associated with more alcohol use [8], with correlations found between increased binge drinking during the pandemic and concomitant depressive symptoms [9].
Individuals with disabilities have historically faced barriers to accessing healthcare, resulting in health inequity, particularly among racial/ethnic minority groups [10]. The COVID-19 pandemic has magnified these longstanding inequities [11]; persons with disabilities are at higher risk of serious illness secondary to underlying neurologic conditions [12,13] and have more difficulty engaging in COVID-19 preventative measures [14]. Persons with traumatic brain injury (TBI) represent an estimated 11.4 million persons with disability [15] who may be particularly affected by the pandemic, though currently only one cross-sectional study exists on how the COVID-19 pandemic has affected TBI survivors [16].
People who have incurred a TBI experience higher rates of depression [17][18][19] and anxiety [20][21][22] relative to individuals without a TBI. One large TBI study found cumulative prevalence of any psychiatric diagnosis (including depression, anxiety, and substance use disorders) was between 30-50% [23]. Presence of depression, anxiety, and/or at-risk substance use (including alcohol) has been linked to poorer physical, cognitive, and functional outcomes post-TBI [24][25][26].
It is unknown if the COVID-19 pandemic has exacerbated at-risk alcohol use or mood disorders among individuals with TBI. Given the high base rates of alcohol use and mood disorders among persons with TBI, distinction between "typical" TBI trajectory and pandemic-induced changes is necessary for any causal interpretation of the impact of the pandemic. Using a difference-in-difference (DiD) analytic approach, the present study aimed to elucidate the impact of the COVID-19 pandemic on alcohol use, depressive and anxiety symptoms among individuals living with TBI. In addition, given emerging evidence of health disparities [27,28] and racial/ethnic differences in alcohol use and psychological distress during the pandemic [4,5,29], we evaluated whether the pandemic differentially affected demographic subgroups with TBI.

Participants
We drew our sample from the Traumatic Brain Injury Model Systems (TBIMS) National Database. This longitudinal database follows persons with a moderate-to-severe TBI at 1, 2, 5, and every subsequent 5 years after injury until death, 16+ years old, have sustained a moderate or severe TBI, and received inpatient rehabilitation at a TBIMS center. TBIMS participants provide informed consent directly or by proxy, and the study is overseen by each TBIMS center's institutional review board.
For the current study, we selected participants, or their proxies, who had completed year 1 (Y1) and year 2 (Y2) post-injury follow-up interviews between October 2, 2017 and January 15, 2021. We defined our primary study exposure, "pandemic-exposed", as participants with TBI who completed their Y1 post-injury interview before January 1, 2020 and their Y2 interview during the COVID-19 pandemic; and "unexposed" as those who completed both Y1 and Y2 interviews before January 1, 2020. We operationally defined the start of the pandemic as April 1, 2020, as this conservatively represented a point in time by which most regions of the U.S. were impacted by the pandemic. January 1, 2020-March 30, 2020 was considered an ambiguous period with regard to pandemic exposure; participants interviewed during this period were excluded for the purposes of our analyses. Thus, there were 1,059 participants with eligible follow-up interviews. Of these, n = 694 (66%) were pandemic-unexposed and n = 365 (34%) were pandemic-exposed (Fig 1 for the timeline of Y1 and Y2 interview dates for pandemic-unexposed and pandemic-exposed participants). We also provide a flow diagram showing the derivation of the analytic sample in Fig 2. The sample with PHQ-9 and GAD-7 was lower than the sample with alcohol use variables because mood measures could only be completed by participants with TBI, while alcohol use could be reported by either participant or proxy.

Measures
Alcohol use. We determined alcohol use by asking participants (or their proxy) if they (the participant) had at least one drink in the month prior to the interview and the number of days per week or month these beverages were consumed. For those who reported drinking, they were asked how many drinks on average were ingested on days they drank. A 'drink' was operationally defined as one can or bottle of beer, glass of wine, can or bottle of wine cooler, cocktail, or shot of liquor. In accordance with the National Institute on Alcohol Abuse and Alcoholism (NIAAA) [30] definition of binge drinking, participants (or their proxy) were asked how many times during the past month they consumed 5+ drinks (males) or 4+ drinks (females) on one occasion. From these questions, we constructed the following outcomes: past month any drinking (y/n), average number of drinks per drinking occasion, and past month binge drinking (y/n).
Depression. We used the Patient Health Questionnaire-9 (PHQ-9) to assess depressive symptom severity. We calculated a total score by summing each of the PHQ-9 items (range 0-27) with higher scores indicating greater depressive symptomatology. The criterion, construct, and external validity of the PHQ-9 have been well established using large samples from a range of patient populations including individuals with moderate-severe TBI [19,31,32].
Anxiety. We measured anxiety symptom severity using the Generalized Anxiety Disorder 7-item scale (GAD-7). The GAD-7 is a self-report screening questionnaire of generalized anxiety symptom severity [33]. We calculated a total score by summing each of the GAD-7 items (range 0-21) with higher scores indicating the presence of greater anxiety symptoms.
Covariates. We included the following sociodemographic covariates: age at injury, racial/ ethnic identity, educational attainment, and primary rehabilitation payor source. We considered these injury-related characteristics: mechanism of injury, time to follow motor commands, time until emergence of post-traumatic amnesia, and pre-index TBI history (i.e., injuries prior to the incident TBI that qualified the individual for TBIMS participation). We included the following clinical characteristics: acute and rehabilitation lengths of stay, cranial surgery status, residential status after rehabilitation discharge, and Functional Independence Measure (FIM) scores at rehabilitation discharge.

Statistical analysis
We used the quasi-experimental DiD design for this secondary analysis of the TBIMS National Database. DiD models are a well-established methodology used in public health, economics, and program evaluation [34][35][36]. This method compares longitudinal panel data between an exposed group and a counterfactual, unexposed group [36].
We constructed a series of DiD models using longitudinal generalized estimating equation (GEE) regression for all outcomes (alcohol use, depressive and anxiety symptoms), which facilitate estimation of population-average marginal effects while accounting for within-subject We created two, mutually-exclusive pandemic exposure groups from Y1 and Y2 post-TBI data from the TBIMS National Database. The pandemic unexposed group had both their Y1 and Y2 interviews prior to January 1, 2020. While, the pandemic exposed group had their Y1 interview prior to January 1, 2020, and their Y2 interview between April 1 st , 2020 and January 15 th , 2021.
https://doi.org/10.1371/journal.pone.0266422.g001 correlation of repeated observations from the same participant. Each model included a DiD coefficient, a follow-up period by pandemic exposure interaction representing differences in outcome scores over time modified by pandemic status. We adjusted GEE models for the covariates age, sex, race, and time to follow commands. For any alcohol use and binge drinking outcomes, we used GEE models with a binary distribution and logit link. For average number of drinks, we used GEE models with a negative binomial distribution with log link. For continuous outcomes of depressive symptoms (PHQ-9 total) and anxiety symptoms (GAD-7 total), we used GEE models with a Gaussian distribution and identity link. For all models, we used the margins and marginsplot commands in STATA 16.1 [37] to plot the predictions from the GEE model fit by pandemic status and follow-up period to illustrate the DiD trend for each outcome.
Subgroup analyses. We conducted pre-specified subgroup analyses by age (± 65 years old), sex, and race/ethnicity (White, Black, and Hispanic ethnicity). For Hispanic subgroup analyses, we included participants if they identified as Hispanic on the race/ethnicity question and/or a separate TBIMS question about Hispanic origin [38]. For each subgroup, we ran the same GEE models as primary analysis that included the follow-up period by pandemic exposure interaction, and adjusted for the same covariates (except those directly stratified on). For age-stratified models (± 65 years old), we controlled for chronological age to adjust for any residual confounding.
Checking assumptions and biases. There are fundamental assumptions underlying DiD models to facilitate causal interpretation [36]. Detailed explanation of our methods, which used historical TBIMS data from 2015-2016 to check the assumption of parallel trend, are provided in S1 Methods. Briefly, this assumption states that, in the absence of exposure, the exposed and unexposed groups would follow the same trajectory of outcome. Of note, the parallel trend assumption does not presuppose that exposure groups be balanced on outcome variables at baseline (e.g., Y1). We also compared those with Y1 data and missing Y2 data to the analytic sample to evaluate any potential selection biases due to attrition at Y2. Sensitivity analyses. We conducted sensitivity analyses of the primary models for any alcohol use, average number of drinks, and binge drinking by excluding persons who were pre-injury alcohol abstainers to test whether conclusions were similar among a subsample of pre-injury drinkers.

Sample characteristics by exposure status
The sample consisted of 1,059 participants with moderate-severe TBI (n = 694 pandemic-unexposed; n = 365 pandemic-exposed) (see Table 1). The pandemic-exposed group was largely similar to the pandemic-unexposed group in demographic, injury, and clinical characteristics.

Evaluating model assumptions and potential biases
Historical TBIMS data provided us with reasonable confidence that parallel trend assumptions were satisfied for all outcomes in our primary sample and all tested subgroups (S1-S17 Figs).
Those lost to follow-up were slightly older, more often had public insurance, more likely injured in a fall, were less likely to have a pre-index TBI history, and had lower FIM Cognitive scores at inpatient rehabilitation discharge than those followed. However, those lost to followup did not significantly differ from the analytic sample on any alcohol use or mood variables at Y1 post-injury (S1 Table).
For depressive symptoms, there was insufficient evidence that the DiD parameters were significant among any age, sex, or race/ethnicity subgroups (S5 Table). For anxiety symptoms, among Hispanics, persons who were exposed to the pandemic had on average a 2.4-point greater increase in their GAD-7 total scores from Y1 to Y2 compared to changes over time among Hispanics unexposed to the pandemic (β = 2.35, 95% CI: 0.25, 4.47, p = 0.028). No other demographic subgroup had statistically significant differences in their anxiety scores over time by exposure group (S6 Table).

Sensitivity analyses
Sensitivity analyses in which we excluded persons who were pre-injury alcohol abstainers showed findings largely similar to the primary alcohol use analyses (S7 Table). Abbreviations: Patient Health Questionnaire-9, PHQ-9; Generalized Anxiety Disorder-7, GAD-7; Difference-in-Difference, DiD ¥ Descriptive measure, not model-based or adjusted for covariates Estimate represents pandemic exposure � followup period interaction parameter estimate from GEE Model with Gaussian distribution and identity link. The GEE model adjusted for age at injury, sex, race, and time to follow commands in days (interpreted as DiD in PHQ-9/GAD-7 between pandemic exposed vs. unexposed from year 1 to year 2). § Estimate represents pandemic exposure � followup period interaction parameter estimate from GEE Model with binomial distribution and logit link. The GEE model adjusted for age at injury, sex, race, and time to follow commands in days (interpreted as DiD in any alcohol use/any binge drinking between pandemic exposed vs. unexposed from year 1 to year 2). € Estimate represents pandemic exposure � followup period interaction parameter estimate from GEE Model with negative binomial distribution and log link. The GEE model adjusted for age at injury, sex, race, and time to follow commands in days (interpreted as DiD in average number of drinks consumed per occasion between pandemic exposed vs. unexposed from year 1 to year 2). https://doi.org/10.1371/journal.pone.0266422.t002

Discussion
Given that individuals with disabilities have been found to be differentially impacted by the COVID-19 pandemic [12][13][14], individuals with moderate-to-severe TBI may be susceptible to direct and/or indirect effects of the COVID-19 pandemic. However, few studies to date have investigated how the pandemic has affected persons with TBI. The current study used a novel quasi-experimental DiD design to evaluate how alcohol use and mood among individuals with TBI has changed as a result of the pandemic, including an evaluation of the pandemic's impact on demographic subgroups. Our data indicated that the average number of drinks per occasion increased more from Y1 to Y2 post-injury among pandemic-exposed persons with TBI compared to those unexposed. The largest increases were seen among males, persons under 65 years old, and Black or Hispanic racial/ethnic minorities. We did not find evidence of differences in the rate of engaging in any alcohol use or past month binge drinking from Y1 to Y2 by pandemic exposure. This is consistent with research [39] from the early months of the pandemic which found that adults consumed more drinks per day in April 2020 compared to February 2020; yet, unlike this prior study, we did not observe increases in binge drinking during the pandemic for persons with moderate-to-severe TBI.
Our study findings suggest factors associated with the pandemic and the context in which people were drinking may have facilitated increases in the quantity of drinks consumed during a typical drinking occasion. We speculate these changes reflect a convergence of factors such as social distancing measures during the pandemic that resulted in more drinking at home without worrying about driving home safely, purchasing alcohol in larger quantities due to availability concerns or to reduce shopping trips during the pandemic, or relaxing of state alcohol purchasing policies during the pandemic (e.g., increases in alcohol delivery options, restaurants being allowed to provide take-home alcohol with orders) [40]. While beyond the data that we had available in this study, it is likely some individuals had increases in occasions of solitary drinking during the pandemic due to the stay-at-home orders and most social activities being cancelled. Solitary drinking has unique risks for experiencing alcohol consequences or developing an alcohol use disorder [41,42].
The psychological and social impact of living through the pandemic has been evident in studies in the general population [8,[43][44][45][46][47], and recent work has shown that one-third of individuals with TBI have identified mental health challenges and social isolation as key barriers to effective coping with the COVID-19 pandemic [16]. The Household Pulse Survey [48] found that anxiety has been particularly high among Hispanic adults and minority racial groups, and also for persons with a disability [48]. Data from the Centers for Disease Control and Prevention revealed that Hispanic adults reported more psychosocial distress than non-Hispanic adults during the pandemic due to instability in housing and food, and death of a loved one [45]. Similarly, in our study, we found that the pandemic resulted in increasing anxiety symptoms particularly among Hispanic persons with TBI. Though we did not observe populationlevel differences in mood by pandemic exposure in our study, mental health should still be continually monitored in TBI populations moving forward. Individuals with moderate-tosevere TBI already struggle with anxiety [49], loneliness [50], and limited social participation compared to non-injured peers [51,52]. These daily challenges would likely only worsen during a global pandemic due to fear of contracting the virus and recommendations or mandates to limit in-person social interaction. Among the reasons for decreased socialization are difficulty navigating masked social interactions [16] and barriers to the use of on-line technology platforms [53,54] for socialization. These new challenges, superimposed on the already existing challenges in this area faced by individuals with TBI, would only add to the mental health challenges characteristic of the COVID-19 pandemic.
The pattern of subgroup findings reported here--specifically, that the largest increases in average drinks per occasion were among Black or Hispanic racial/ethnic minorities, together with substantial increases in anxiety symptoms among Hispanic individuals exposed to the pandemic--may suggest that factors other than the pandemic played a role in the differences observed. Previous research has found Black/non-Hispanic adults and Hispanic women have had the largest increases in alcohol consumption during the pandemic, consuming more drinks per day than White, non-Hispanic adults, with the exception of women with children under 5 years old [39]. And alcohol consumption is inextricably linked with anxiety [55]. The political and sociocultural climate in the U.S. during the pandemic can be characterized by political discord and heightened racial tensions, and it will be impossible to disentangle the relative contributions of multiple stressors on the results observed herein. However, the observation that racial and ethnic minorities with TBI who were exposed to the pandemic experienced greater increases in alcohol use and anxiety may reflect disproportionately detrimental ambient stress and related consequences during the time period studied.
The TBIMS offers a unique opportunity to understand the impact of the pandemic on individuals with TBI because we have data on the same participants before and after pandemic and are able to compare this change to an unexposed comparison group with harmonized measures. However, there are some limitations in both the data available and our analysis approach. Though our binge drinking measure was consistent with NIAAA guidelines, we did not have information available in this study on alcohol use disorder nor, more generally, consequences of drinking. We were unable to determine whether participants had COVID-19, and did not have measures on the mediating psychosocial factors (e.g., loss of a loved one, discrimination) that may explain our results. The DiD approach requires non-missing data from Y1 and Y2, so it is possible that the most depressed/anxious individuals were not captured at Y2 due to higher attrition; however, this limitation is ameliorated by there being no significant differences in Y1 alcohol use and depression/anxiety between the analytic sample and those without Y2 data. Finally, consistent with other studies [27,28,45,48], findings from our study highlight how systemic factors (e.g., access to healthcare and technology) affect individuals with TBI and from racial and ethnic minority groups. Though we did not have data available to measure these factors directly, this is an important area for future study.

Conclusions
The current findings indicating an increase in the number of drinks consumed on a typical drinking occasion and anxiety suggest we should monitor alcohol consumption and mental health among individuals with TBI as the pandemic unfolds. In particular, adherence to lowrisk drinking guidelines [56] for individuals with TBI can help mitigate future risk for substance use disorders [57].